tbuckley/cabot-search huggingface dataset:
A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer
Authors: Zoe June F. Assaf, Wei Zou, Alexander D. Fine, Mark A. Socinski, Amanda Young, Doron Lipson, Jonathan F. Freidin, Mark Kennedy, Eliana Polisecki, Makoto Nishio, David Fabrizio, Geoffrey R. Oxnard, Craig Cummings, Anja Rode, Martin Reck, Namrata S. Patil, Mark Lee, David S. Shames, Katja Schulze
Journal: Nature Medicine (2023)

One of the great challenges in therapeutic oncology is determining who might achieve survival benefits from a particular therapy. Studies on longitudinal circulating tumor DNA (ctDNA) dynamics for the prediction of survival have generally been small or nonrandomized. We assessed ctDNA across 5 time points in 466 non-small-cell lung cancer (NSCLC) patients from the randomized phase 3 IMpower150 study comparing chemotherapy-immune checkpoint inhibitor (chemo-ICI) combinations and used machine learning to jointly model multiple ctDNA metrics to predict overall survival (OS). ctDNA assessments through cycle 3 day 1 of treatment enabled risk stratification of patients with stable disease (hazard ratio (HR) = 3.2 (2.0-5.3), P < 0.001; median 7.1 versus 22.3 months for high- versus low-intermediate risk) and with partial response (HR = 3.3 (1.7-6.4), P < 0.001; median 8.8 versus 28.6 months). The model also identified high-risk patients in an external validation cohort from the randomized phase 3 OAK study of ICI versus chemo in NSCLC (OS HR = 3.73 (1.83-7.60), P = 0.00012). Simulations of clinical trial scenarios employing our ctDNA model suggested that early ctDNA testing outperforms early radiographic imaging for predicting trial outcomes. Overall, measuring ctDNA dynamics during treatment can improve patient risk stratification and may allow early differentiation between competing therapies during clinical trials.
Exhausted intratumoral Vδ2− γδ T cells in human kidney cancer retain effector function
Authors: Chiara Rancan, Marcel Arias-Badia, Pranay Dogra, Brandon Chen, Dvir Aran, Hai Yang, Diamond Luong, Arielle Ilano, Jacky Li, Hewitt Chang, Serena S. Kwek, Li Zhang, Lewis L. Lanier, Maxwell V. Meng, Donna L. Farber, Lawrence Fong
Journal: Nature Immunology (2023)

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2- γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2- γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2- T-cell receptors. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.
Negativity drives online news consumption
Authors: Claire E. Robertson, Nicolas Pröllochs, Kaoru Schwarzenegger, Philip Pärnamets, Jay J. Van Bavel, Stefan Feuerriegel
Journal: Nature Human Behaviour (2023)

Abstract Online media is important for society in informing and shaping opinions, hence raising the question of what drives online news consumption. Here we analyse the causal effect of negative and emotional words on news consumption using a large online dataset of viral news stories. Specifically, we conducted our analyses using a series of randomized controlled trials ( N = 22,743). Our dataset comprises ~105,000 different variations of news stories from Upworthy.com that generated ∼5.7 million clicks across more than 370 million overall impressions. Although positive words were slightly more prevalent than negative words, we found that negative words in news headlines increased consumption rates (and positive words decreased consumption rates). For a headline of average length, each additional negative word increased the click-through rate by 2.3%. Our results contribute to a better understanding of why users engage with online media.
Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells
Authors: Michael Valente, Nils Collinet, Thien-Phong Vu Manh, Dimitri Popoff, Khalissa Rahmani, Karima Naciri, Gilles Bessou, Rejane Rua, Laurine Gil, Cyrille Mionnet, Pierre Milpied, Elena Tomasello, Marc Dalod
Journal: Nature Immunology (2023)

Abstract Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46 GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN + versus IFN − pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.
Partner choice, confounding and trait convergence all contribute to phenotypic partner similarity
Authors: Jennifer Sjaarda, Zoltán Kutalik
Journal: Nature Human Behaviour (2023)

Abstract Partners are often similar in terms of their physical and behavioural traits, such as their education, political affiliation and height. However, it is currently unclear what exactly causes this similarity—partner choice, partner influence increasing similarity over time or confounding factors such as shared environment or indirect assortment. Here, we applied Mendelian randomization to the data of 51,664 couples in the UK Biobank and investigated partner similarity in 118 traits. We found evidence of partner choice for 64 traits, 40 of which had larger phenotypic correlation than causal effect. This suggests that confounders contribute to trait similarity, among which household income, overall health rating and education accounted for 29.8, 14.1 and 11.6% of correlations between partners, respectively. Finally, mediation analysis revealed that most causal associations between different traits in the two partners are indirect. In summary, our results show the mechanisms through which indirect assortment increases the observed partner similarity.
The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences
Authors: Mandy I. Cheng, Joey H. Li, Luke Riggan, Bryan Chen, Rana Yakhshi Tafti, Scott Chin, Feiyang Ma, Matteo Pellegrini, Haley Hrncir, Arthur P. Arnold, Timothy E. O’Sullivan, Maureen A. Su
Journal: Nature Immunology (2023)
IFNγ-induction of TH1-like regulatory T cells controls antiviral responses
Authors: Angela M. Gocher-Demske, Jian Cui, Andrea L. Szymczak-Workman, Kate M. Vignali, Julianna N. Latini, Gwen P. Pieklo, Jesse C. Kimball, Lyndsay Avery, Ellyse M. Cipolla, Brydie R. Huckestein, Lee Hedden, Marlies Meisel, John F. Alcorn, Lawrence P. Kane, Creg J. Workman, Dario A. A. Vignali
Journal: Nature Immunology (2023)
Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity
Authors: Lise Mangiante, Nicolas Alcala, Alexandra Sexton-Oates, Alex Di Genova, Abel Gonzalez-Perez, Azhar Khandekar, Erik N. Bergstrom, Jaehee Kim, Xiran Liu, Ricardo Blazquez-Encinas, Colin Giacobi, Nolwenn Le Stang, Sandrine Boyault, Cyrille Cuenin, Severine Tabone-Eglinger, Francesca Damiola, Catherine Voegele, Maude Ardin, Marie-Cecile Michallet, Lorraine Soudade, Tiffany M. Delhomme, Arnaud Poret, Marie Brevet, Marie-Christine Copin, Sophie Giusiano-Courcambeck, Diane Damotte, Cecile Girard, Veronique Hofman, Paul Hofman, Jérôme Mouroux, Charlotte Cohen, Stephanie Lacomme, Julien Mazieres, Vincent Thomas de Montpreville, Corinne Perrin, Gaetane Planchard, Nathalie Rousseau, Isabelle Rouquette, Christine Sagan, Arnaud Scherpereel, Francoise Thivolet, Jean-Michel Vignaud, Didier Jean, Anabelle Gilg Soit Ilg, Robert Olaso, Vincent Meyer, Anne Boland-Auge, Jean-Francois Deleuze, Janine Altmuller, Peter Nuernberg, Alejandro Ibáñez-Costa, Justo P. Castaño, Sylvie Lantuejoul, Akram Ghantous, Charles Maussion, Pierre Courtiol, Hector Hernandez-Vargas, Christophe Caux, Nicolas Girard, Nuria Lopez-Bigas, Ludmil B. Alexandrov, Françoise Galateau-Salle, Matthieu Foll, Lynnette Fernandez-Cuesta
Journal: Nature Genetics (2023)

Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma
Authors: Marta Larrayoz, Maria J. Garcia-Barchino, Jon Celay, Amaia Etxebeste, Maddalen Jimenez, Cristina Perez, Raquel Ordoñez, Cesar Cobaleda, Cirino Botta, Vicente Fresquet, Sergio Roa, Ibai Goicoechea, Catarina Maia, Miren Lasaga, Marta Chesi, P. Leif Bergsagel, Maria J. Larrayoz, Maria J. Calasanz, Elena Campos-Sanchez, Jorge Martinez-Cano, Carlos Panizo, Paula Rodriguez-Otero, Silvestre Vicent, Giovanna Roncador, Patricia Gonzalez, Satoru Takahashi, Samuel G. Katz, Loren D. Walensky, Shannon M. Ruppert, Elisabeth A. Lasater, Maria Amann, Teresa Lozano, Diana Llopiz, Pablo Sarobe, Juan J. Lasarte, Nuria Planell, David Gomez-Cabrero, Olga Kudryashova, Anna Kurilovich, Maria V. Revuelta, Leandro Cerchietti, Xabier Agirre, Jesus San Miguel, Bruno Paiva, Felipe Prosper, Jose A. Martinez-Climent
Journal: Nature Medicine (2023)

Abstract The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8 + T cells with reduced immunosuppressive regulatory T (T reg ) cells, while late MYC acquisition in slow progressors was associated with lower CD8 + T cell infiltration and more abundant T reg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8 + T cells versus T reg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8 + T/T reg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8 + T cell cytotoxicity or depleting T reg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.
MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation
Authors: Domien Vanneste, Qiang Bai, Shakir Hasan, Wen Peng, Dimitri Pirottin, Joey Schyns, Pauline Maréchal, Cecilia Ruscitti, Margot Meunier, Zhaoyuan Liu, Céline Legrand, Laurence Fievez, Florent Ginhoux, Coraline Radermecker, Fabrice Bureau, Thomas Marichal
Journal: Nature Immunology (2023)

Abstract Resident tissue macrophages (RTMs) are differentiated immune cells that populate distinct niches and exert important tissue-supportive functions. RTM maintenance is thought to rely either on differentiation from monocytes or on RTM self-renewal. Here, we used a mouse model of inducible lung interstitial macrophage (IM) niche depletion and refilling to investigate the development of IMs in vivo. Using time-course single-cell RNA-sequencing analyses, bone marrow chimeras and gene targeting, we found that engrafted Ly6C + classical monocytes proliferated locally in a Csf1 receptor-dependent manner before differentiating into IMs. The transition from monocyte proliferation toward IM subset specification was controlled by the transcription factor MafB, while c-Maf specifically regulated the identity of the CD206 + IM subset. Our data provide evidence that, in the mononuclear phagocyte system, the ability to proliferate is not merely restricted to myeloid progenitor cells and mature RTMs but is also a tightly regulated capability of monocytes developing into RTMs in vivo.
Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial
Authors: Tina Cascone, Cheuk H. Leung, Annikka Weissferdt, Apar Pataer, Brett W. Carter, Myrna C. B. Godoy, Hope Feldman, William N. William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S. Yadav, Frank R. Rojas Alvarez, Younghee Lee, Aditya K. Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V. Negrao, Xiuning Le, Carl M. Gay, Anne S. Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S. Glisson, Frank V. Fossella, Yasir Y. Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Ravi Rajaram, Mara B. Antonoff, Junya Fujimoto, Luisa M. Solis, Edwin R. Parra, Cara Haymaker, Ignacio I. Wistuba, Stephen G. Swisher, Ara A. Vaporciyan, Heather Y. Lin, Jing Wang, Don L. Gibbons, J. Jack Lee, Nadim J. Ajami, Jennifer A. Wargo, James P. Allison, Padmanee Sharma, Humam Kadara, John V. Heymach, Boris Sepesi
Journal: Nature Medicine (2023)

Abstract Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR / ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8 + T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia , and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129 .)
The VISA-A (sedentary) should be used for sedentary patients with Achilles tendinopathy: a modified version of the VISA-A developed and evaluated in accordance with the COSMIN checklist
Authors: Richard Norris, Jill L Cook, Jamie E Gaida, Thomas Maddox, Jaya Raju, Seth O'Neill
Journal: British Journal of Sports Medicine (2023)

To develop and evaluate a modified version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire, for use in sedentary patients with Achilles tendinopathy, using the Consensus-based Standards for the selection of health Measurement Instruments recommendations.Twenty-two sedentary patients with Achilles tendinopathy completed the VISA-A and provided feedback regarding the relevance, comprehensiveness and comprehensibility of each item, response options and instructions. Patient and professional feedback was used to develop the VISA-A (sedentary) questionnaire. Reliability, validity and responsiveness of the VISA-A (sedentary) was evaluated in 51 sedentary patients with Achilles tendinopathy: 47.1% women, mean age 64.8 (SD 11.24).Factor analysis identified two dimensions (symptoms and activity) for the VISA-A (sedentary). Test-retest reliability was excellent for symptoms (intraclass correlation coefficient, ICC=0.991) and activity (ICC=0.999). Repeatability was 1.647 for symptoms and 0.549 for activity. There was a significant difference between the VISA-A and VISA-A (sedentary) scores both pretreatment and post-treatment. There was stronger correlation between the pretreatment to post-treatment change in the VISA-A (sedentary) scores (r=0.420 for symptoms, r=0.407 for activity) and the global rating of change than the VISA-A scores (r=0.253 for symptoms, r=0.186 for activity).The VISA-A (sedentary) demonstrates adequate reliability, validity and responsiveness in sedentary patients with Achilles tendinopathy. The VISA-A (sedentary) is a more appropriate measure than the VISA-A for this cohort and is recommended for clinical and research purposes.
Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology
Authors: Dominik Sturm, David Capper, Felipe Andreiuolo, Marco Gessi, Christian Kölsche, Annekathrin Reinhardt, Philipp Sievers, Annika K. Wefers, Azadeh Ebrahimi, Abigail K. Suwala, Gerrit H. Gielen, Martin Sill, Daniel Schrimpf, Damian Stichel, Volker Hovestadt, Bjarne Daenekas, Agata Rode, Stefan Hamelmann, Christopher Previti, Natalie Jäger, Ivo Buchhalter, Mirjam Blattner-Johnson, Barbara C. Jones, Monika Warmuth-Metz, Brigitte Bison, Kerstin Grund, Christian Sutter, Steffen Hirsch, Nicola Dikow, Martin Hasselblatt, Ulrich Schüller, Arend Koch, Nicolas U. Gerber, Christine L. White, Molly K. Buntine, Kathryn Kinross, Elizabeth M. Algar, Jordan R. Hansford, Nicholas G. Gottardo, Martin U. Schuhmann, Ulrich W. Thomale, Pablo Hernáiz Driever, Astrid Gnekow, Olaf Witt, Hermann L. Müller, Gabriele Calaminus, Gudrun Fleischhack, Uwe Kordes, Martin Mynarek, Stefan Rutkowski, Michael C. Frühwald, Christof M. Kramm, Andreas von Deimling, Torsten Pietsch, Felix Sahm, Stefan M. Pfister, David. T. W. Jones
Journal: Nature Medicine (2023)

The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.
Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment
Authors: Sayali Onkar, Jian Cui, Jian Zou, Carly Cardello, Anthony R. Cillo, Mostofa Rafid Uddin, April Sagan, Marion Joy, Hatice U. Osmanbeyoglu, Katherine L. Pogue-Geile, Priscilla F. McAuliffe, Peter C. Lucas, George C. Tseng, Adrian V. Lee, Tullia C. Bruno, Steffi Oesterreich, Dario A. A. Vignali
Journal: Nature Cancer (2023)
Splenic Arteriovenous Fistula Coexisting With Spontaneous Splenorenal Shunt in a Cirrhotic Patient
Authors: Guofeng Liu, Xiaoze Wang, Xuefeng Luo
Journal: Clinical Gastroenterology and Hepatology (2023)

A 56-year-old man with alcoholic cirrhosis presented with large gastroesophageal varices type 1 and refractory ascites. Abdominal computed tomography angiography with 3-dimensional reconstruction showed early visualization of the branches of the splenic vein in the arterial phase (Figure A, arrow), along with a tortuous collateral vessel originating from the splenic hilum to the left renal vein (Figure A, arrowheads). Splenic arteriography confirmed the computed tomography findings of splenic arteriovenous fistula (SAVF) (Figure B, arrow) and concurrent spontaneous splenorenal shunt (SSRS) (Figure B, arrowheads). The patient received a transjugular intrahepatic portosystemic shunt and endovascular embolization of the SSRS using plugs and remained asymptomatic during a 1-year follow-up period (Figure C). SAVF is a rare condition that eventually will lead to acute portal hypertension. SSRS is an abnormal collateral vessel with a prevalence of 10.5% to 21% among liver cirrhosis patients. To the best of our knowledge, the concurrent presence of SAVF and SSRS is rarely reported. SAVF may aggravate the portal pressure, especially in a patient with cirrhosis. Comprehensive imaging evaluation is important for the proper management of complications of portal hypertension.
Structural and functional asymmetry of the neonatal cerebral cortex
Authors: Logan Z. J. Williams, Sean P. Fitzgibbon, Jelena Bozek, Anderson M. Winkler, Ralica Dimitrova, Tanya Poppe, Andreas Schuh, Antonios Makropoulos, John Cupitt, Jonathan O’Muircheartaigh, Eugene P. Duff, Lucilio Cordero-Grande, Anthony N. Price, Joseph V. Hajnal, Daniel Rueckert, Stephen M. Smith, A. David Edwards, Emma C. Robinson
Journal: Nature Human Behaviour (2023)